Background: Medication non-adherence is a significant contributor to healthcare inefficiency, resulting in poor medication management, impaired patient outcomes and ineffective symptom control. This review summarises interventions targeting medication adherence for adults with mental-physical multimorbidity, in primary healthcare settings. Methods: A systematic review of literature was conducted using Medline, Embase, PsycInfo, Web of Science, Cochrane Library, and CINAHL were searched for relevant studies. Data were extracted and synthesized using narrative synthesis. The Cochrane Effective Practice and Organisation of Care (EPOC) was used to classify intervention types. Risk of bias was assessed using the National Heart, Lung, and Blood Institute (NHLBI) quality assessment tool. Results: Eleven studies representing 2,279 patients were included. All interventions examined were classified into one EPOC domain, which was delivery arrangements. All included studies examined patients with a physical condition, alongside depression. Seven studies examining coordination of care and management of care processes interventions reported significant improvements in medication adherence attributed to the intervention. Four studies considering the use of information and communication technology observed no changes in medication adherence. Conclusion: Interventions that coordinate and manage healthcare processes may help improve how patients adhere to their medication regimes, particularly in patients with mental-physical multimorbidity. However, we still need to better understand how digital health technology can support patients in following their medication regimes. As we face the growing challenges of treating multimorbidity, everyone involved in health services - from providers to policymakers - must be receptive to a more integrated approach to the delivery of healthcare.